This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Attachment to DAC-TG application for Chromatin Modeling Project NYU Computer Access Request The primary focus of the research involves the way DNA folds within the nucleus. This is important because it influences both replication and transcription processes. The study seeks to elucidate complex folding mechanisms of DNA and protein into compact chromatin fibers. This research requires computer resources to run Monte Carlo simulations of a mesoscopic model of chromatin to elucidate the detailed mechanism by which chromatin compacts. Previous simulation work has validated the chromatin model by reproducing experimentally observed effects of salt concentration on sedimentation coefficients. These sophisticated simulations have also been used to understand the dynamics of chromatin unfolding and folding as a result of post-translation chemical modifications of flexible histone tails. The model has recently been advanced to incorporate effects of divalent ions such as magnesium which decreases the persistence link of DNA so that it can bend more tightly. Other advancements include incorporations of linker histones into the chromatin fiber to investigate their role in compaction at a geometrical and energetic level. Early simulation results have shown that magnesium and linker histones dramatically impact the geometries with the result of highly compacted fibers, which is in line with experimental findings. The next step in the project is to investigating the role of DNA linker length, i.e. the distance between nucleosomes. Such studies could provide fundamental insights into the structure of the 30-nanometer fiber, whose basic geometric organization is still the subject of debate. Recent experimental studies have shown a peculiar dependence of fiber width on DNA linker length. It will be important to more thoroughly investigate the effects of DNA linker length on chromatin fibers using our robust theoretical model because it can provide valuable geometric insights at smaller resolution than is currently available experimentally. Resource Details: Proposed Simulations: 10 linker length sizes 10 array length sizes 6 starting structures 10 random seeds 10 sets of deltas 4 sets: +H1+Mg, +H1-Mg, -H1+Mg, and H1-Mg Total: Up to 240,000 simulations CPU usage per simulation: 200-2000 hours This research is conducted under the supervision of Dr. Tamar Schlick. Dr. Schlick holds joint appointments in the NYU Chemistry Department and the Courant Institute of Mathematical Sciences.